Cells You Can See: A Profile of Art Olson

By Madeline McCurry-Schmidt

Cells are bafflingly complex.

“If you think about Manhattan—and all the people in Manhattan—and try to figure out what each person is doing and their interactions with each other at every moment… that is not as complex as a cellular environment,” said Art Olson, professor at The Scripps Research Institute (TSRI).

To better understand this mind-boggling tangle, Olson’s lab creates models and computer programs to help scientists visualize cells, viruses and other biological players.

If scientists can figure out how proteins and other molecules interact, they can design new drugs and therapies. Already, Olson’s work has led to advances in HIV and tuberculosis research.

“Understanding how biology works at all levels helps us understand how to keep people well and how to cure people who are sick,” said Olson.

Biology Becomes Art

Olson’s strategy is to approach biological modeling from every angle possible. In his molecular graphics laboratory, researchers employ the same programs used in video game design to model colorful, richly textured biological structures.

His lab members also use more traditional, hands-on techniques. One lab member, TSRI Associate Professor David Goodsell, paints watercolors of structures such as red blood cells and organisms such as E. coli.

By turning scientific images into works of art, Olson’s laboratory brings biology to new audiences. In 2013, dance students at the University of Michigan set Goodsell’s images to music and turned cellular processes into choreography for a performance called “Autophagy.” And in 2014, two digital images created in his lab were exhibited at the San Diego International Airport as part of show, “Taking Art to the Cellular Level.”

Olson was also an early adopter of 3D printing, in which layered blots of ink harden into a model. Models in hand, researchers can visualize individual atoms in an antibody, for example.

This kind of visualization is possible with computer imaging, but Olson believes physical models have some advantages. With some of the physical models developed in the lab, one can instantly tweak the positions of molecules; one can even twist and fold proteins to see how a changing structure might affect function.

Take the eye-catching DNA model in Olson’s office. Colorful chunks of plastic make up the ladder-rung base pairs. The Olson lab designed the double-stranded model with magnets, so it can unzip like actual DNA. Play with the model, and the magnets meet with a satisfying “snap!”

When one of Olson’s TSRI colleagues left a few years ago to teach at the Bishop’s School in La Jolla, California, he brought models like this with him. The students loved them, and the lab has since tried designing models for use in schools. Olson is now working with an educational research institute, WestEd, in the Bay Area to test some of these models in high schools.

“These physical models are great teaching tools,” said Olson.

In fact, last summer TSRI Professor Erica Ollmann Saphire, a leading Ebola virus researcher and Olson’s frequent collaborator, kept one of Olson’s models on hand to show TV viewers nationwide exactly how an experimental Ebola treatment attached to the virus.

“The Olson lab models are intuitive and clear,” said Saphire. “They allow us to immediately explain the meaning of a structure to the public and to other scientists.”

Indeed, Olson has found that scientists like having physical models on hand. “It gives them a different view of the molecules they’re studying,” said Olson. “You can play with it in your hands, just like Watson and Crick played with their DNA model 60 years ago.”

Modeling Fights Disease

Olson’s inspiration to improve human health began with a plane flight.

In the late 1960s, Olson joined the Peace Corps and was sent to teach science in a village in Ghana. The village had no phone lines, and only one store there had electricity.

(Always a creative thinker, Olson ran power lines over the road to borrow electricity from the store for the enlarger in his photography dark room—a necessity for the village school’s photography club—which he started.)

What really struck Olson in this new environment was the need for better public health. For example, he saw that unsafe water sources led to cholera.

Today, Olson’s lab designs computational programs that researchers use with the goal of improving human health around the world. One useful program is Autodock, which takes the structure of a molecule and simulates how it would bind, or “dock,” with a protein. The program can test how drug molecules dock with and disable HIV, for example.

“We now know a lot about the molecular biology of HIV. We know where the weak spots are, and we can try to target them,” said Olson. When they find a molecule “hit” that binds with the virus in Autodock, Olson’s lab alerts chemists and biologists who can test the molecule in the laboratory.

Autodock is freely available to researchers around the world, and Olson estimates that the program has been used in at least 30,000 labs. The program is useful, but scientists can been limited by computer processing time. When Olson first started working on Autodock, it took about 20 minutes for a computer to run one docking simulation between a molecule and a disease target.

That all changed about 10 years ago, when Olson teamed up with tech giant IBM to run Autodock on the World Community Grid, a network of more than three million computers around the world. These are computers in homes and offices of people, not necessarily scientists, who go to worldcommunitygrid.org and volunteer their computer’s free time to run docking simulations and other programs. These programs are safe and do not interfere with the computer’s normal functions.

The World Community Grid provides processing power never seen before. Today, instead of spending 20 minutes on one docking simulation, the World Community Grid can test thousands of dockings in less than a minute.

“Now we can screen millions of molecules to look for the needle in the haystack,” said Olson.

Olson has so far used the World Community Grid to test molecules that could fight HIV, malaria and Ebola virus.

This data sometimes points to unexpected findings. Olson’s lab recently reported that anti-malaria simulations on the World Community Grid had identified two compounds that might be used to fight drug-resistant tuberculosis.

“It’s always a great feeling to know that what you do is actually impacting the world,” said Olson.

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“Understanding how biology works at all levels helps us understand how to keep people well and how to cure people who are sick,” says Professor Art Olson, whose lab takes many different approaches to molecular modeling. (Photo by Cindy Brauer.)